It is extremely difficult to obtain a chemical agent which will successfully image in the brain. The agent must pass through the blood brain barrier and then be retained in the brain. Although there are many compositions which do pass through the blood brain barrier there are very few that do not quickly clear from the brain by passing back through the blood brain barrier. It is theorized that in order for an agent to remain within the brain to provide a successful image some chemical alteration of the agent must occur within the brain.
Hexamethylpropylene diamine oxime (4,8,-diaza-3,6,6,9-tetramethyl undecane-2,10-dione bisoxime) hereinafter referred to as HM--PAO has been found to be very useful as a brain perfusion imaging agent. It is believed that the inherent instability of HM--PAO ligated to 99m-technetium in some way causes this agent to be chemically altered in the brain. Thus, 99m-Tc HM--PAO passes through the blood brain barrier, is theoretically altered in some way, and remains in the brain for a period of time sufficient to obtain a successful brain image.
There are several patents which discuss and disclose this composition. For example, Troutner et al U.S. Pat. No. 4,615,876, European Patent Application No. 0 179 608 published Apr. 30, 1986, European Patent Application No. 0 123 504 published Oct. 31, 1984 and U.S. Pat. No. 4,789,736. Unfortunately, the in vivo instability of this composition which makes it a successful brain imaging agent also makes it a very unstable composition in vitro. In an article entitled "Kinetic Analysis of Technetium-99m D,1-HM--PAO Decomposition in Aqueous Media," J. Nucl. Med., 29:1568-1576, 1988, it is reported that although the aqueous in vitro degradation rate of this complex is slow the instability of the technetium bonded HM--PAO in vitro requires that it be administered within 30 minutes of its formulation. In the proceedings of the 35th Annual Meeting of the J. Nucl. Med., Vol. 29, No. 5, May, 1988 it is reported that the technetium complex of the HM--PAO can be stabilized by using gentisic acid within the first 30 seconds after formation of the technetium complex. However, even with this modification, this radiopharmaceutical must be used within hours after preparation.